Percutaneously Implantable Replacement Heart Valve Device and Method of Making Same

ABSTRACT

A method of making a replacement heart valve device whereby a fragment of biocompatible tissue material is treated and soaked in one or more alcohol solutions and a solution of glutaraldehyde. The dried biocompatible tissue material is folded and rehydrated in such a way that forms a two- or three-leaflet/cusp valve without affixing of separate cusps or leaflets or cutting slits into the biocompatible tissue material to form the cusps or leaflets. After the biocompatible tissue material is folded, it is affixed at one or more points on the outer surface to the inner cavity or a stent.

CONTINUITY INFORMATION

The present application is a continuation application of U.S. patentapplication Ser. No. 13/675,665 filed on Nov. 13, 2012, which is acontinuation application of U.S. patent application Ser. No. 10/887,688filed on Jul. 10, 2004, now U.S. Pat. No. 8,308,797, which is acontinuation-in-part application of U.S. patent application Ser. No.10/037,266, filed on Jan. 4, 2002 (now abandoned). All of the foregoingapplications are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is in the field of heart valve replacement. Morespecifically, the present invention is directed to a method of making apercutaneously implantable replacement heart valve.

2. Description of Related Art

There have been numerous efforts in the field of heart valve replacementto improve both the durability and effectiveness of replacement heartvalves as well as the ease of implantation. A brief description of heartvalves and heart function follows to provide relevant background for thepresent invention.

There are four valves in the heart that serve to direct the flow ofblood through the two sides of the heart in a forward direction. On theleft (systemic) side of the heart are: 1) the mitral valve, locatedbetween the left atrium and the left ventricle, and 2) the aortic valve,located between the left ventricle and the aorta. These two valvesdirect oxygenated blood coming from the lungs through the left side ofthe heart into the aorta for distribution to the body. On the right(pulmonary) side of the heart are: 1) the tricuspid valve, locatedbetween the right atrium and the right ventricle, and 2) the pulmonaryvalve, located between the right ventricle and the pulmonary artery.These two valves direct de-oxygenated blood coming from the body throughthe right side of the heart into the pulmonary artery for distributionto the lungs, where it again becomes re-oxygenated to begin the circuitanew.

Heart valves are passive structures that simply open and close inresponse to differential pressures on either side of the particularvalve. They consist of moveable “leaflets” that are designed simply toopen and close in response to differential pressures on either side ofthe valve's leaflets. The mitral valve has two leaflets and thetricuspid valve has three. The aortic and pulmonary valves are referredto as “semilunar valves” because of the unique appearance of theirleaflets, which are more aptly termed “cusps” and are shaped somewhatlike a half-moon. The aortic and pulmonary valves each have three cusps.

In general, the components of heart valves include the valve annulus,which will remain as a roughly circular open ring after the leaflets ofa diseased or damaged valve have been removed; leaflets or cusps;papillary muscles which are attached at their bases to the interiorsurface of the left or right ventricular wall; and multiple chordaetendineae, which couple the valve leaflets or cusps to the papillarymuscles. There is no one-to-one chordal connection between the leafletsand the papillary muscles; instead, numerous chordae are present, andchordae from each papillary muscle attach to both of the valve leaflets.

When the left ventricular wall relaxes so that the ventricular chamberenlarges and draws in blood, the leaflets of the mitral valve separateand the valve opens. Oxygenated blood flows in a downward directionthrough the valve, to fill the expanding ventricular cavity. Once theleft ventricular cavity has filled, the left ventricle contracts,causing a rapid rise in the left ventricular cavitary pressure. Thiscauses the mitral valve to close while the aortic valve opens, allowingthe oxygenated blood to be ejected from the left ventricle into theaorta. The chordae tendineae of the mitral valve prevent the mitralleaflets from prolapsing back into the left atrium when the leftventricular chamber contracts.

The three leaflets, chordae tendineae, and papillary muscles of thetricuspid valve function in a similar manner, in response to the fillingof the right ventricle and its subsequent contraction. The cusps of theaortic valve also respond passively to pressure differentials betweenthe left ventricle and the aorta. When the left ventricle contracts, theaortic valve cusps open to allow the flow of oxygenated blood from theleft ventricle into the aorta. When the left ventricle relaxes, theaortic valve cusps reapproximate to prevent the blood which has enteredthe aorta from leaking (regurgitating) back into the left ventricle. Thepulmonary valve cusps respond passively in the same manner in responseto relaxation and contraction of the right ventricle in movingde-oxygenated blood into the pulmonary artery and thence to the lungsfor re-oxygenation. Neither of these semilunar valves has associatedchordae tendineae or papillary muscles.

Problems that can develop with heart valves consist of stenosis, inwhich a valve does not open properly, and/or insufficiency, also calledregurgitation, in which a valve does not close properly. In addition tostenosis and insufficiency of heart valves, heart valves may need to besurgically repaired or replaced due to certain types of bacterial orfungal infections in which the valve may continue to function normally,but nevertheless harbors an overgrowth of bacteria (vegetation) on theleaflets of the valve that may embolize and lodge downstream in a vitalartery. If such vegetations are on the valves of the left side (i.e.,the systemic circulation side) of the heart, embolization may occur,resulting in sudden loss of the blood supply to the affected body organand immediate malfunction of that organ. The organ most commonlyaffected by such embolization is the brain, in which case the patientsuffers a stroke. Thus, surgical replacement of either the mitral oraortic valve (left-sided heart valves) may be necessary for this problemeven though neither stenosis nor insufficiency of either valve ispresent. Likewise, bacterial or fungal vegetations on the tricuspidvalve may embolize to the lungs resulting in a lung abscess andtherefore, may require replacement of the tricuspid valve even though notricuspid valve stenosis or insufficiency is present.

These problems are treated by surgical repair of valves, although oftenthe valves are too diseased to repair and must be replaced. If a heartvalve must be replaced, there are currently several options available,and the choice of a particular type of artificial valve depends onfactors such as the location of the valve, the age and other specificsof the patient, and the surgeon's experiences and preferences. Currentlyin the United States over 100,000 defective heart valves are replacedannually, at an approximate cost of $30-50,000 per procedure, and thusit would be desirable if heart valves could be replaced using minimallyinvasive techniques and without having to repeat the procedure within amatter of years due to the lack of durability of the replacement heartvalve. It would be especially advantageous if a defective heart valvecould be removed via an endovascular procedure, that is, a procedurewhere the invasion into the body is through a blood vessel such as thefemoral artery. The procedure is then carried out percutaneously andtransluminally using the vascular system to convey appropriate devicesto the position in the body wherein it is desired to carry out thedesired procedure. An example of such a procedure would be angioplasty,wherein a catheter carrying a small balloon at its distal end ismanipulated through the body's vessels to a point where there is ablockage in a vessel. The balloon is expanded to create an opening inthe blockage, and then the balloon is deflated and the catheter andballoon are removed from the vessel.

Endovascular procedures have substantial benefits both from thestandpoint of health and safety as well as cost. Such procedures requireminimal invasion of the human body, and there is consequentlyconsiderable reduction and in some instances even elimination, of theuse of a general anesthesia and much shorter hospital stays.

Replacement heart valves can be categorized as either artificialmechanical valves, transplanted valves and tissue valves. Replacementheart valves are designed to optimize hemodynamic performance,thrombogenicity and durability. Another factor taken into considerationis the relative ease of surgical implantation.

Mechanical valves are typically constructed from nonbiological materialssuch as plastics, metals and other artificial materials which, whiledurable, are expensive and prone to blood clotting which increases therisk of an embolism. Anticoagulants taken to help against blood clottingcan further complicate the patient's health due to increased risks forhemorrhages.

Transplanted valves are natural valves taken from cadavers. These valvesare typically removed and frozen in liquid nitrogen, and are stored forlater use. They are typically fixed in glutaraldehyde to eliminateantigenicity and are sutured in place, typically with a stent.

Artificial tissue valves are valves constructed from animal tissue, suchas bovine or porcine tissue. Efforts have also been made at using tissuefrom the patient for which the valve will be constructed.

Most tissue valves are constructed by sewing the leaflets of pig aorticvalves to a stent to hold the leaflets in proper position, or byconstructing valve leaflets from the pericardial sac of cows or pigs andsewing them to a stent. The porcine or bovine tissue is chemicallytreated to alleviate any antigenicity. The pericardium is a membranethat surrounds the heart and isolates it from the rest of the chest wallstructures. The pericardium is a thin and very slippery, which makes itdifficult for suturing in a millimetricly precise way. The method ofmaking the replacement heart valve of the present invention solves thisproblem through a process that includes drying and compressing thepericardium using photo-mechanical compression in such a way that makesit possible to handle and fold the material more easily.

For example, one prior replacement heart valve requires each sculptedleaflet to be trimmed in a way that forms an extended flap, whichbecomes a relatively narrow strand of tissue near its tip. The tip ofeach pericardial tissue strand is sutured directly to a papillarymuscle, causing the strand to mimic a chordae tendineae. Each strandextends from the center of a leaflet in the valve, and each strand issutured directly to either an anterior and posterior papillary muscle.This requires each leaflet to be positioned directly over a papillarymuscle. This effectively rotates the leaflets of the valve about 90degrees as compared to the leaflets of a native valve. The line ofcommissure between the leaflets, when they are pressed together duringsystole, will bisect (at a perpendicular angle) an imaginary line thatcrosses the peaks of the two papillary muscles, instead of lying roughlyalong that line as occurs in a native valve.

A different approach to creating artificial tissue valves is describedin U.S. Pat. No. 5,163,955 to Calvin, et al. and U.S. Pat. Nos.5,571,174 and 5,653,749 to Love. Using a cutting die, the pericardialtissue is cut into a carefully defined geometric shape, treated withglutaraldehyde, then clamped in a sandwich-fashion between two stentcomponents. This creates a tri-leaflet valve that resembles an aortic orpulmonary valve, having semilunar-type cusps rather thanatrioventricular-type leaflets.

U.S. Pat. No. 3,671,979 to Moulopoulos describes an endovascularlyinserted conical shaped umbrella-like valve positioned and held in placeby an elongated mounting catheter at a supra-annular site to the aorticvalve in a nearby arterial vessel. The conical end points toward themalfunctioning aortic valve and the umbrella's distal ends open upagainst the aorta wall with reverse blood flow, thereby preventingregurgitation.

U.S. Pat. No. 4,056,854 to Boretos describes an endovascularly inserted,catheter mounted, supra-annular valve in which the circular frame abutsthe wall of the artery and attached flaps of flexible membrane extenddistally in the vasculature. The flaps lie against the artery wallduring forward flow, and close inward towards the central catheter toprevent regurgitation during reverse blood flow. The Boretos valve wasdesigned to be positioned against the artery wall during forward flow,as compared to the mid-center position of the Moulopoulos valve, toreduce the stagnation of blood flow and consequent thrombus and embolicformation expected from a valve at mid-center position.

The main advantage of tissue valves is that they do not cause bloodclots to form as readily as do the mechanical valves, and therefore,they do not absolutely require systemic anticoagulation. The majordisadvantage of tissue valves is that they lack the long-term durabilityof mechanical valves. Tissue valves have a significant failure rate,usually within ten years following implantation. One cause of thesefailures is believed to be the chemical treatment of the animal tissuethat prevents it from being antigenic to the patient. In addition, thepresence of extensive suturing prevents the artificial tissue valve frombeing anatomically accurate in comparison to a normal heart valve, evenin the aortic valve position.

A shortcoming of prior artificial tissue valves has been the inabilityto effectively simulate the exact anatomy of a native heart valve.Although transplanted human or porcine aortic valves have the grossappearance of native aortic valves, the fixation process (freezing withliquid nitrogen, and chemical treatment, respectively) alters thehistologic characteristics of the valve tissue. Porcine and bovinepericardial valves not only require chemical preparation (usuallyinvolving fixation with glutaraldehyde), but the leaflets must besutured to cloth-covered stents in order to hold the leaflets inposition for proper opening and closing of the valve. Additionally, theleaflets of most such tissue valves are constructed by cutting orsuturing the tissue material, resulting in leaflets that do notduplicate the form and function of a real valve and are more susceptibleto failure.

SUMMARY OF THE INVENTION

The present invention is a replacement heart valve device and method ofmaking same. The replacement heart valve device, in a preferredembodiment, comprises a stent made of stainless steel or self-expandingnitinol and a completely newly designed artificial biological tissuevalve disposed within the inner space of the stent. The cusp or leafletportion of the valve means is formed by folding of the pericardiummaterial preferably used to create the valve without cutting of slits toform leaflets or suturing or otherwise affixing of separate leafletportions. Other forms of tissue and suitable synthetic materials canalso be used for the valve, formed in a sheet of starting material. Thefolded design provides a number of advantages over prior designs,including improved resistance to tearing at suture lines. Thecusps/leaflets open in response to blood flow in one direction and closein response to blood flow in the opposite direction. Preferably thetubular portion of the valve means contains the same number of cusps asthe native valve being replaced, in substantially the same size andconfiguration. The outer surface of the valve means is attached to thestent member.

The replacement heart valve device is preferably implanted using adelivery system having a central part which consists of a flexiblehollow tube catheter that allows a metallic guide wire to be advancedinside it. The stented valve is collapsed over the central tube and itis covered by a movable sheath. The sheath keeps the stented valve inthe collapsed position. Once the cover sheath is moved backwards, thestented valve can be deployed. The endovascular stented-valve, in apreferred embodiment, is a glutaraldehyde fixed mammal pericardium orsynthetic biocompatible material which has two or three cusps that opendistally to permit unidirectional blood flow. The stent can either beself-expanding or the stent can be expandable through use of a ballooncatheter.

The present invention also comprises a method of making a replacementheart valve device. In order to make the valve, the pericardium startingmaterial is isolated and all the fat tissue and extra fibers areremoved. The biological membrane material is cleaned by mechanicalseparation of unwanted layers using hydromechanical force means. Oncethe pericardium is completely clean, the material is dried in order tomake it easier to handle and fold. Preferably, this drying is done byexposing the biocompatible membrane material to photomechanicalcompression to remove all lipids from the pericardium or otherbiocompatible membrane material and to cause protein denaturalization,transforming the material into a stronger and more homogeneous surface.The valve is formed by taking a flat sheet of the material and foldingin such a way that forms a three-leaflet or other number of leafletvalve. Then it is placed in a sequence of solutions, one of isopropylalcohol of about 70-100%, one of ethanol of about 70-100%, one ofglycerol and one of glutaraldehyde, preferably at a concentration ofabout 0.07-25% for approximately 36 hours. The material is dried inorder to make it easier to handle and fold. Preferably this drying isdone by exposing the biocompatible membrane material to light and thenmechanically compressing the material to cause protein denaturation.This results in material that is stronger and more homogeneous. Thevalve is formed by taking a flat sheet of bovine or porcine pericardiumand folding it in such a way that forms a three-leaflet valve. The valvecan also be made in the same manner from fresh, cryopreserved orglutaraldehyde fixed allografts or xenografts or syntheticnon-biological, non-thrombogenic material. The folding of thepericardium material to create the cusps or leaflets reduces the extentof suturing otherwise required, and resembles the natural form andfunction of the valve leaflets. The cleaning, pressing and dryingtechnique used to create the valve material makes the folding morepracticable. The valve is rehydrated after being formed. The method ofthe present invention also greatly reduces the risk of tearing of thecusps or leaflets, since they are formed by folding a single uncutportion of material forming the valve rather than being attached bysuturing.

Once the endovascular implantation of the prosthetic valve device iscompleted in the host, the function of the prosthetic valve device canbe monitored by the same methods as used to monitor valve replacementsdone by open heart surgery. Routine physical examination, periodicechocardiography or angiography can be performed. In contrast to openheart surgery, however, the host requires a short recovery period andcan return home within one day of the endovascular procedure. Thereplacement heart valve device of the present invention can be used inany patient where bioprosthetic valves are indicated, namely elderlypatients with cardiac valve diseases, and patients unable to tolerateopen heart procedures or life-long anticoagulation medication andtreatment. The present invention can be practiced in applications withrespect to each of the heart's valves.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a side perspective view of the replacement heart valvedevice of the present invention in one embodiment with the valve in theclosed position.

FIG. 2 depicts the folds which form the leaflets or cusps of thereplacement heart valve of the present invention in one embodiment.

FIGS. 3A and 3B depict a preferred procedure for folding the pericardiumtissue starting material to create the replacement heart valve of thepresent invention.

FIG. 4 depicts a side perspective view of the replacement heart valvedevice of the present invention in one embodiment represented as ifimplanted within an artery.

FIG. 5 depicts a side view of one embodiment of the replacement heartvalve device of the present invention mounted within a self-expandingstent, with the stent in the expanded position.

FIG. 6 depicts a side perspective view of one embodiment of thereplacement heart valve device of the present invention mounted within aself-expanding stent in the collapsed position.

FIG. 7 depicts the suture points of one embodiment of the replacementheart valve device of the present invention.

FIG. 8 depicts the implantation/delivery system used with the presentinvention in a preferred embodiment.

FIGS. 9A, 9B and 9C depict a representation of a sheet of biocompatiblevalve material showing preferred folds.

DESCRIPTION OF A PREFERRED EMBODIMENT

The present invention comprises a percutaneously implantable replacementheart valve and a method for making same. The artificial heart valvedevice of the present invention is capable of exhibiting a variablediameter between a compressed or collapsed position and an expandedposition. A preferred embodiment of the replacement heart valve deviceaccording to the present invention is set forth in FIG. 5. Thereplacement heart valve device comprises a stent member 100 and aflexible valve means 200. The stent member 100 is preferablyself-expanding, although balloon-expandable stents can be used as well,and has a first polygonal shape in its compressed or collapsedconfiguration and a second, larger polygonal shape in its expandedconfiguration. Referring to FIG. 1, the valve means 200 comprises agenerally tubular portion 210 and, preferably, a peripheral upstandingcusp or leaflet portion 220. The valve means 200 is disposed within thecylindrical stent member 100 with the tubular portion 210 transverse ofand at some acute angle relative to the stent walls. The diameter of thetubular portion 210 is substantially the same as the inside diameter ofthe stent member in its initial expanded configuration. The peripheralupstanding cusp or leaflet portion 220 is disposed on valve means 200substantially parallel to the walls of the stent member similar to acuff on a shirt. The cusp or leaflet portion 220 of the valve means 200is generally tubular in shape and comprises three leaflets 221, 222 and223 as shown, although it is understood that there could be from two tofour leaflets. The tubular portion of the valve means 200 is attached tothe stent member 100 by a plurality of sutures 300, as depicted in FIG.7.

The leaflet portion 220 of the valve means 200 extends across ortransverse of the cylindrical stent 100. The leaflets 221, 222 and 223are the actual valve and allow for one-way flow of blood. The leafletportion 220 as connected to the rest of the valve resembles the cuff ofa shirt. FIG. 9 depicts the folds preferred for valve cusp and leafletformation involving three leaflets. The configuration of the stentmember 100 and the flexible, resilient material of construction allowsthe valve to collapse into a relatively small cylinder as seen in FIG.6. The replacement heart valve will not stay in its collapsedconfiguration without being restrained. Once the restraint is removed,the self-expanding stent member 100 will cause the artificial heartvalve to take its expanded configuration, as seen in FIG. 5.

Stent Member

The stent member 100 preferably comprises a self-expandingnickel-titanium alloy stent, also called “nitinol,” in a sine wave-likeconfiguration as shown in FIG. 5. An enlarged view of a preferredembodiment of the stent member for use in the replacement heart valve ofthe invention is depicted in FIG. 5. The stent member 100 includes alength of wire 110 formed in a closed zigzag configuration. The wire canbe a single piece, stamped or extruded, or it could be formed by weldingthe free ends together. The straight sections of the stent member 100are joined by bends. The stent is readily compressible to a smallcylindrical shape as depicted in FIGS. 6 and 8, and resilientlyself-expandable to the shape shown in FIG. 5.

The stent member 100 of the artificial heart valve device of the presentinvention may be made from various metal alloys, titanium, titaniumalloy, nitinol, stainless steel, or other resilient, flexible non-toxic,non-thrombogenic, physiologically acceptable and biocompatiblematerials. The configuration may be the zigzag configuration shown or asine wave configuration, mesh configuration or a similar configurationwhich will allow the stent to be readily collapsible andself-expandable. When a zigzag or sine wave configured stent member isused, the diameter of the wire from which the stent is made ispreferably from about 0.010 to 0.035 inches and still, preferably fromabout 0.012 to 0.025 inches. The diameter of the stent member will befrom about 1.5 to 3.5 cm, preferably from about 1.75 to 3.00 cm, and thelength of the stent member will be from about 1.0 to 10 cm, preferablyfrom about 1.1 to 5 cm.

The stent used in a preferred embodiment of the present invention isfabricated from a “shaped memory” alloy, nitinol, which is composed ofnickel and titanium. Nitinol wire is first fashioned into the desiredshape for the device and then the device is heat annealed. A meshwork ofnitinol wire of approximately 0.008 inch gauge is formed into a tubularstructure with a minimum central diameter of 20 mm to make the stent.Away from its central portion, the tubular structure flares markedly atboth ends in a trumpet-like configuration. The maximum diameter of theflared ends of the stent is approximately 50 mm. The purpose of thestent is to maintain a semi-rigid patent channel through the diseasedcardiac valve following its implantation.

When the components of the replacement heart valve device are exposed tocold temperatures, they become very flexible and supple, allowing themto be compressed down and pass easily through the delivery sheath. Acold temperature is maintained within the sheath during delivery to thedeployment site by constantly infusing the sheath with an iced salinesolution. Once the valve components are exposed to body temperature atthe end of the sheath, they instantaneously reassume their predeterminedshapes, thus allowing them to function as designed.

Preferably the stent member 100 carries a plurality of barbs extendingoutwardly from the outside surface of the stent member for fixing theheart valve device in a desired position. More preferably the barbs aredisposed in two spaced-apart, circular configurations with the barbs inone circle extending in an upstream direction and the barbs in the othercircle extending in a downstream direction. It is especially preferablethat the barbs on the inflow side of the valve point in the direction offlow and the barbs on the outflow side point in the direction oppositeto flow. It is preferred that the stent be formed of titanium alloy wireor other flexible, relatively rigid, physiologically acceptable materialarranged in a closed zigzag configuration so that the stent member willreadily collapse and expand as pressure is applied and released,respectively.

Valve Means

The valve means 200 is flexible, compressible, host-compatible, andnon-thrombogenic. The valve means 200 can be made from variousmaterials, for example, fresh, cryopreserved or glutaraldehyde fixedallografts or xenografts. Synthetic biocompatible materials such aspolytetrafluoroethylene, polyester, polyurethane, nitinol or otheralloy/metal foil sheet material and the like may be used. The preferredmaterial for the valve means 200 is mammal pericardium tissue,particularly juvenile-age animal pericardium tissue. The valve means 200is disposed within the cylindrical stent member 100 with the tubularportion 210 transverse of and at some acute angle relative to the stentwalls. The diameter of the tubular portion 210 is substantially the sameas the inside diameter of the stent member 100 in its initial expandedconfiguration. The peripheral upstanding cusp or leaflet portion 220 isdisposed substantially parallel to the walls of the stent member 100similar to a cuff on a shirt.

The cusp or leaflet portion 220 of the valve means 200 is formed byfolding of the pericardium material used to create the valve. FIGS. 3Aand 3B depict the way the sheet of heart valve starting material isfolded. The starting material is preferably a flat dry sheet, which canbe rectangular or other shaped. The cusps/leaflets 221, 222 and 223 openin response to blood flow in one direction and close in response toblood flow in the opposite direction. Preferably the cusp or leafletportion 220 of the valve means 200 contains the same number of cusps asthe native valve being replaced, in substantially the same size andconfiguration. FIGS. 9A-9C depict a preferred configuration for folds tocreate the leaflets/cusps. The leaflet forming portion is a single,continuous, uncut layer affixed to the interior of the cuff layer toform the leaflets/cusps, unlike prior efforts that have involvedsuturing of three separate leaflet/cusp portions onto the main valvebody portion. The leaflets are formed from the free edge of the materialafter forming the cuff portion. Referring now to FIGS. 9-A, 9B, and 9C,with flat sheet on a table, a person facing the sheet would create acuff at the upper border of sheet by folding the horizontal top edgeaway/downwardly (fold no. 1). The leaflet portion is formed by foldingthe sheet's lower half towards the folder/upwardly, as shown in FIG. 9A(fold no. 2). The sheet, now with the upper cuff and bottom inward fold,is folded inwardly at two preferably equidistant vertical points asshown in FIG. 9B to create the leaflet/cusp portion (folds nos. 3 and4). The leaflets/cusps are formed by folding fold nos. 6, 7 and 8 afterthe two opposite vertical edges of sheet are joined to create acylindrical valve shape, depicted in FIGS. 1 and 3B. The inner leafletlayer is preferably attached to the outer cuff layer by curved orstraight continuous suturing. Although a preferred embodiment of theinvention comprises a single piece of valve material folded to createthe valve body and a leaflet-forming portion that has no cuts orsutures, the inventors have discovered that as long as the leafletportion of the valve itself is formed from a single piece ofbiocompatible valve material, the other portions of the valve can beformed by suturing of one or more separate pieces of material withoutlosing the novel and improved qualities of the present invention. Thisallows for the valve to be made even stronger, more durable and easierto make. This alternate embodiment comprises a leaflet forming layermade of a single piece of valve material attached to a separate pieceforming the valve body having a folded cuff portion. The single pieceleaflet forming layer is preferably cylindrical in shape and can beformed with or without folding. In this embodiment the single pieceleaflet layer can itself be attached to the stent with or without acylindrical cuff portion. Attachment is preferably by suturing,particularly continuous single or double sutures.

Method of Making Replacement Heart Valve Device

The present invention also comprises a method of making a replacementheart valve device. In order to make the valve, the biocompatible tissuematerial is isolated and all the fat tissue and extra fibers areremoved. Cleaning is preferably accomplished by using a hydromechanicalforce-based cleaning device to separate tissue layers and hydration withdistilled water to remove unwanted layers. Once the pericardium iscompletely clean, it is subjected to photo-mechanical compression, thenthe valve is formed and placed in sequential solutions of isopropylalcohol of about 70-100%, ethanol of about 70-100%, glycerol andglutaraldehyde preferably at a concentration of about 0.07-25% for about36 hours, respectively. The material is preferably photomechanicallycompressed to remove lipids and produce protein coagulation to make thesurface smoother and more compact and biocompatible, decreasing themolecular distance of collagen fibers. The exposure to light andmechanical compression cause protein denaturation making the materialstronger and more homogeneous and biocompatible. Gas sterilization canalso be used to sterilize the tissue membrane material. The valve isformed by taking a flat sheet of the material and folding it in such away that forms a three-leaflet or desired number of leaflet valve asshown in FIGS. 3A and 3B and/or FIGS. 9A, 9B and 9C. The folding of thepericardium material to create the cusps or leaflets reduces the extentof suturing otherwise required, and resembles the natural form andfunction of the valve leaflets. It also greatly reduces the risk oftearing of the cusps or leaflets, since they are integral to the valverather than being attached by suturing.

In a preferred embodiment, the single continuous piece of membrane isfolded inward to form an inner leaflet layer within the outer cuff. Thesingle leaflet layer is then attached to the cuff layer to form valvecusps in one of three preferred ways: (i) by curved or straightcontinuous single or double sutures that affix and form the bases orrecesses of the valve cusps; (ii) by lengthwise suture lines attachingthe leaflet layer to the cuff layer with the bases or recesses of thevalve cusps being thus formed of the folded edge of the membrane; (iii)by further folding of the membrane into lengthwise pleats secured bylengthwise suture attaching the leaflet layer to the cuff layer with thebases or recesses of the valve cusps being thus formed of the foldededge of the membrane, done for the purpose of giving greater strengthand durability to the attachment points of the leaflet layer.

In order to make the pericardium material less slippery and easier tofold, the pericardium is dried, preferably with artificial light using amulti-watt lamp with the pericardium or other biocompatible membranematerial placed in a flat aluminum surface to dry it homogeneously. Aphotomechanical drying machine can also be used. The final result is ahomogeneous tissue that looks like plastic paper and makes it easy tomanipulate to fold and suture the valve. Once the valve is formed, it isre-hydrated by placing it in a solution of water and 70% alcohol. Inapproximately 3 days the valve is fully rehydrated. The suturing ofmembrane layers to form the valve is done with single, double, or morecontinuous suture material. This form of suturing has great advantagesfor durability and avoidance of damage to the membrane and can beperformed by sewing machines. The attachment points of the leaflet layerto the cuff layer may be reinforced by folding an additional layer ofmembrane over the attachment point before suturing, this layer beingformed of a projected tab of the continuous piece of leaflet membrane.The free edge of the leaflet layer may be straight or curved, and thisfree edge forming the free edges of the individual leaflets may becontoured in parabolic or curved shape.

Attachment of the Valve Means to the Stent Member

The valve means 200 is then attached to the inner channel of the stentmember 100 by suturing the outer surface of the valve means' pericardiummaterial to the stent member. FIG. 7 depicts preferred suture points ofone embodiment of the present invention: 3-point fixation or 6-pointfixation at each border of the stent. Other fixation schemes can beutilized, such as, by way of non-limiting example, fixation on bothborders 18 points at each end following a single plane and 36 fixationpoints following to adjacent vertical planes. The use of only one planeof fixation points helps prevent systolic collapse of the proximal edgeof the valve means. A fold on the border of the pericardium materialprevents tearing. The attachment position of the valve is preferablycloser to the proximal and wider part of the stent.

The sequence of steps can vary. The pericardium material can be fixed inglutaraldehyde before attachment to the stent or the valve can be formedand then fixed with glutaraldehyde after mounting it in the stent. Oneobservation noted is that the material becomes whiter and apparentlyincreases its elasticity. 1 mm vascular clips keep the cusps coaptedwhile fixing them in glutaraldehyde. The use of metallic clips to keepboth cusps adjacent to each other after 24 hours of fixation inglutaraldehyde helps to educate the material and make the primaryposition of the valve cusps adjacent to each other. After the clips areremoved, there are no lesions to the valve.

Different suture materials can be used, including, in a preferredembodiment, Prolene 1-0 to 8-0 and Mersilene 1-0 to 8-0 which is abraided suture.

Implantation of Replacement Heart Valve Device

The replacement heart valve device of the present invention ispreferably used in surgical procedures involving the percutaneous andtransluminal removal of the diseased or defective heart valve and thepercutaneous and transluminal implantation of the new heart valvedescribed above. The defective heart valve is removed by a suitablemodality, such as, for example, laser, ultrasound, mechanical, or othersuitable forms of delivery of energy, or phacoemulsion, including, butnot limited to, laser lithotripsy, mechanical lithotripsy,electrohydraulic lithotripsy, and laser or mechanical ablation. Toremove the native heart valve that is being replaced, a guidewire isinserted percutaneously and transluminally using standard vascular orangiography techniques. The distal end of the guidewire is manipulatedto extend through and across the defective heart valve. Then a catheteris advanced distally through the femoral artery to a point proximal tothe defective heart valve, between the origin of the coronary artery andthe origin of the right subclavian artery. The position of the distalend of catheter can be monitored by observation of radiopaque markers.Collector member is preferably inflated and occludes the aorta at apoint between the origin of the coronary artery and the right subclavianartery. Next, a balloon and cutting tool are advanced through thecatheter so that the cutting tool and uninflated balloon are distal tothe defective heart valve. Optionally an additional step, such asballoon dilatation or atherectomy, may be required to provide apassageway through the heart valve. A catheter is also placed into thecoronary sinus via a transjugular puncture. This catheter is used forinfusion of blood or cardioplegia solution during the portion of theprocedure when the aorta is occluded. The absence of valves in thecardiac venous system allows retrograde flow so that there will be aneffluence of fluid from the coronary arteries. This flow of fluid isdesired to prevent embolization of material into the coronary arteriesduring the procedure. Once the cutting tool is in place, the balloon isinflated and flexible shaft is rotated. Once the cutting tool hasreached the appropriate rotation speed, the cutting tool is pulledproximally to remove the defective heart valve. The balloon and thecutting tool are spaced apart so that the inflated balloon will bestopped by the perimeter, unremoved portion of the defective heartvalve, which will signal the physician that the valve has been removed,as well as protect the heart and aorta from damage from the valveremoval device. Once it is determined that the defective heart valve hasbeen removed, the cutting tool is slowed or stopped altogether and theballoon is deflated. The cutting tool and the deflated balloon arepulled proximally through catheter. Then, a catheter containing anartificial heart valve is inserted and the artificial heart valve isplaced as described above.

The delivery and implantation system of the replacement artificial heartvalve of the present invention percutaneously and transluminallyincludes a flexible catheter 400 which may be inserted into a vessel ofthe patient and moved within that vessel as depicted in FIG. 8. Thedistal end 410 of the catheter 400, which is hollow and carries thereplacement heart valve device of the present invention in its collapsedconfiguration, is guided to a site where it is desired to implant thereplacement heart valve. The catheter has a pusher member 420 disposedwithin the catheter lumen 430 and extending from the proximal end 440 ofthe catheter to the hollow section at the distal end 410 of thecatheter. Once the distal end 410 of the catheter is positioned asdesired, the pusher mechanism 420 is activated and the distal portion ofthe replacement heart valve device is pushed out of the catheter and thestent member 100 partially expands. In this position the stent member100 is restrained so that it doesn't pop out and is held for controlledrelease, with the potential that the replacement heart valve device canbe recovered if there is a problem with the positioning. The catheter400 is then retracted slightly and the replacement heart valve device iscompletely pushed out of the catheter 400 and released from the catheterto allow the stent member 100 to fully expand. If the stent member 100preferably includes two circles of barbs on its outer surface aspreviously described, the first push and retraction will set one circleof barbs in adjacent tissue and the second push and release of thereplacement heart valve device will set the other circle of barbs inadjacent tissue and securely fix the replacement heart valve device inplace when the device is released from the catheter.

Alternatively, or in combination with the above, the replacement heartvalve device could be positioned over a metallic guidewire that isadvanced through the catheter. The replacement heart valve device of thepresent invention is preferably implanted percutaneously through anaortic passageway to, or near to, the location from which the naturalheart valve has been removed. Referring to FIG. 8, the implantationsystem comprises a flexible hollow tube catheter 410 with a metallicguide wire 450 disposed within it. The stented valve device is collapsedover the tube and is covered by a moveable sheath 460. The moveablesheath 460 maintains the stented valve device in the collapsed position.The implantation method comprises the following steps: inserting thereplacement heart valve device in the lumen of a central blood vesselvia entry through the brachial or femoral artery using a needle orexposing the artery surgically; placing a guide wire 450 through theentry vessel and advancing it to the desired position; advancingdilators over the wire to increase the lumen of the entry site, therebypreparing the artery to receive the heart-valve; and advancing theheart-valve device to the desired place. The stented-valve device isreleased by pulling the cover sheath 460 of the delivery system allowingthe self-expanding stent to achieve its full expansion. A balloonexpandable stent can alternately be used to deliver the valve to itsdesired position. At this point, a pigtail catheter is advanced over thewire and an aortogram is performed to assess the competency of thevalve.

Before creation of the valve means and implantation, the patient isstudied to determine the architecture of the patient's heart. Usefultechniques include fluoroscopy, transesophageal echocardiography, MRI,and angiography. The results of this study will enable the physician todetermine the appropriate size for the replacement heart valve.

In one procedure for implantation of the replacement heart valve deviceof the present invention, the femoral artery of the patient is canulatedusing a Cook needle and a standard J wire is advanced into the arteryeither percutaneously or after surgical exposure of the artery. An 8 Fintroducer is advanced into the femoral artery over the wire. The J wireis then withdrawn and anticoagulation is started using heparin 60 U/Kgintravenously. Once vascular access is obtained an aortogram isperformed for anatomical evaluation. A special wire (Lunderquist orAmplatz superstiff) is advanced into the aortic arch and dilatorsprogressively larger are advanced over the wire, starting with 12 F allthe way to 18 F. After this the valve introducer device containing theprosthetic valve device is then inserted and used to transport thereplacement valve over a guidewire to the desired position. Thestented-valve is released by pulling the cover sheath of the deliverysystem allowing the self-expanding stent to achieve its full expansion.At this point, a pigtail catheter is advanced over the wire and repeataortogram is performed to assess the competency of the valve.

When the device is used to treat severe leakage of the aortic valve, thenative valve is left in place and the prosthetic stented valve isdeployed below the subclavian artery. When the device is used to treataortic stenosis, first the stenotic valve needs to be opened usingeither aortic valvuloplasty or cutting and if this procedure inducesaortic insufficiency the stented valve is placed to prevent theregurgitation.

Intravascular ultrasound or an angioscope passed intravascularly viaeither the venous system through the intra-atrial septum across themitral valve and into the left ventricle or retrograde via the femoralartery would provide the added benefit of allowing constant highdefinition imaging of the entire procedure and high flow irrigation.

Once the endovascular implantation of the prosthetic valve device iscompleted in the host, the function of the prosthetic valve device canbe monitored by the same methods as used to monitor valve replacementsdone by open heart surgery. Routine physical examination, periodicechocardiography or angiography can be performed. In contrast to openheart surgery, however, the host requires a short recovery period andcan return home within one day of the endovascular procedure. Theprosthetic valve device can be used in any patient where bioprostheticvalves are indicated, namely elderly patients with cardiac valvediseases, and patients unable to tolerate open heart procedures orlife-long anticoagulation. In addition, with the development oflonger-life, flexible, non-thrombogenic synthetic valve alternatives tobioprosthesis, the prosthetic valve device will be indicated in allpatients where the relative advantages of the life-span, thenon-thrombogenic quality, and the ease of insertion of prosthetic valvedevices outweigh the disadvantages of mechanical valves. Anticoagulationmay be beneficial in certain clinical situations for either short orlong term use.

This method of percutaneous endovascular heart-valve replacement, incontrast to open heart surgical procedures, requires only localanesthesia, partial or no cardiac bypass, one to two dayshospitalization, and should result in a reduced mortality rate ascompared to open heart procedures.

While the present invention has been shown and described herein in whatis considered to be a preferred embodiment thereof, illustrating theresults and advantages over the prior art obtained through the presentinvention, the invention is not limited to the specific embodimentsdescribed above. Thus, the forms of the invention shown and describedherein are to be taken as illustrative and other embodiments may beselected without departing from the spirit and scope of the presentinvention.

1.-33. (canceled)
 34. A percutaneously implantable replacement heartvalve, comprising: a stent member having an inner channel, the stentmember collapsible, expandable and configured for percutaneous delivery,wherein the stent member includes a tubular structure away from itscentral portion that flares at both ends in a trumpet-like configurationsuch that the inner channel has a larger diameter at both ends than asmaller diameter located at the central portion of the stent member; andan outer cuff layer and an inner leaflet layer attached to the stentmember, the inner leaflet layer including individual leaflets.
 35. Thepercutaneously implantable replacement heart valve of claim 34, whereinthe individual leaflets reside radially inward from the outer cufflayer.
 36. The percutaneously implantable replacement heart valve ofclaim 34, wherein each of the individual leaflets is bounded bylengthwise-oriented lines of sutures.
 37. The percutaneously implantablereplacement heart valve of claim 36, wherein a crease is located betweenthe individual leaflets and the outer cuff layer at a base of theindividual leaflets.
 38. The percutaneously implantable replacementheart valve of claim 34, wherein the outer cuff layer is sutured to theinner leaflet layer at a base of the individual leaflets.
 39. Thepercutaneously implantable replacement heart valve of claim 34, whereinthe outer cuff layer is connected to the inner leaflet layer to form asheet of material.
 40. The percutaneously implantable replacement heartvalve of claim 34, wherein the outer cuff layer and the inner leafletlayer comprise a single continuous sheet of material.
 41. Thepercutaneously implantable replacement heart valve of claim 34, whereinthe outer cuff layer and the inner leaflet layer are made of abiocompatible material.
 42. The percutaneously implantable replacementheart valve of claim 41, wherein the biocompatible material comprises atreated pericardium tissue.
 43. The percutaneously implantablereplacement heart valve of claim 41, wherein the biocompatible materialcomprises a synthetic material.
 44. The percutaneously implantablereplacement heart valve of claim 34, wherein the outer cuff layer andthe inner leaflet layer are contiguous and reside as a single elemententirely within the inner channel of the stent member.
 45. Thepercutaneously implantable replacement heart valve of claim 34, whereinthe stent member is fabricated from nitinol.
 46. A percutaneouslyimplantable replacement heart valve, comprising: a stent member that isboth collapsible and expandable, wherein the stent member is configuredfor percutaneous delivery, wherein the stent member includes a tubularstructure away from its central portion that flares at both ends in atrumpet-like configuration; and an outer cuff layer and an inner leafletlayer attached to the stent member, the inner leaflet layer includingtwo to four individual leaflets, wherein each individual leaflet of thetwo to four leaflets is rectangular in shape in side elevation view. 47.The percutaneously implantable replacement heart valve of claim 46,wherein each of the two to four leaflets is bounded bylengthwise-oriented lines of sutures.
 48. The percutaneously implantablereplacement heart valve of claim 47, wherein a crease is located betweenthe inner leaflet layer and the outer cuff layer at a base of the two tofour individual leaflets.
 49. The percutaneously implantable replacementheart valve of claim 46, wherein the outer cuff layer is sutured to theinner leaflet layer at a base of the two to four individual leaflets.50. The percutaneously implantable replacement heart valve of claim 46,wherein the outer cuff layer is connected to the inner leaflet layer toform a sheet of material.
 51. The percutaneously implantable replacementheart valve of claim 46, wherein the outer cuff layer and the innerleaflet layer comprise a single continuous sheet of material.
 52. Thepercutaneously implantable replacement heart valve of claim 46, whereinthe outer cuff layer and inner leaflet layer are made of a biocompatiblematerial.
 53. The percutaneously implantable replacement heart valve ofclaim 52, wherein the biocompatible material comprises a treatedpericardium tissue.
 54. The percutaneously implantable replacement heartvalve of claim 52, wherein the biocompatible material comprises asynthetic material.
 55. A percutaneously implantable replacement heartvalve for implantation in a patient, comprising: a stent member havingan inner channel, the stent member collapsible, expandable andconfigured for percutaneous delivery, wherein the stent member includesa tubular structure away from its central portion that flares at bothends in a trumpet-like configuration; and a valve means residingentirely within the inner channel of the stent member, the valve meansincluding an outer cuff layer and two to four individual leaflets,wherein each of the two to four individual leaflets is rectangular inshape in side elevation view, and wherein after implantation in thepatient, the valve means resides as a single element entirely within theinner channel of the stent member, and wherein only the two to fourindividual leaflets reside radially inward from the outer cuff layer.56. The percutaneously implantable replacement heart valve of claim 55,wherein each of the two to four individual leaflets is bounded bylengthwise-oriented lines of sutures.
 57. The percutaneously implantablereplacement heart valve of claim 56, wherein a crease is located betweenthe two to four individual leaflets and the outer cuff layer at a baseof the two to four individual leaflets.
 58. The percutaneouslyimplantable replacement heart valve of claim 55, wherein the outer cufflayer is sutured to the two to four individual leaflets at a base of thetwo to four individual leaflets.
 59. The percutaneously implantablereplacement heart valve of claim 55, wherein the outer cuff layer isconnected to the two to four individual leaflets to form a sheet ofmaterial.
 60. The percutaneously implantable replacement heart valve ofclaim 55, wherein the outer cuff layer and the two to four individualleaflets comprise a single continuous sheet of material.
 61. Thepercutaneously implantable replacement heart valve of claim 55, whereinthe outer cuff layer and the two to four individual leaflets are made ofa biocompatible material.
 62. The percutaneously implantable replacementheart valve of claim 61, wherein the biocompatible material comprises atreated pericardium tissue.
 63. The percutaneously implantablereplacement heart valve of claim 61, wherein the biocompatible materialcomprises a synthetic material.